Methadone: Safer Than Opiates for Chronic Pain?



NEW ORLEANS – Physicians are feeling the heat over the highly publicized national public health crisis stemming from overprescribing oxycodone for non-cancer chronic pain. One result has been a huge shift to using methadone for that indication. But is that the answer?

Methadone is widely perceived as an attractive alternative to oxycodone because it’s less euphoria-inducing and thus somewhat less prone to abuse, as well as less expensive. But the reality is it’s a very tricky drug to use safely for pain management, according to Dr. Barak Gaster, a general internist at the University of Washington, Seattle.

Methadone is a highly unusual opiate. The dose-response relationship is far more variable and idiosyncratic than for oxycodone or other opiates. Methadone has numerous active metabolites. And as those active metabolites accumulate during the first 2 weeks on any given dose of the drug, patients will gradually experience greater analgesia and, disturbingly, more respiratory depression as well.

"This is one of the most dangerous situations for unintentional overdose. Patients have to understand that this is kind of a dangerous medication, and it’s going to take a couple weeks to kick in during which it’s absolutely essential that they don’t increase the dose on their own," Dr. Gaster explained at the annual meeting of the American College of Physicians.

The other major shortcoming of methadone as a treatment for chronic pain is that the drug comes in big-dose tablets designed for once-daily treatment of heroin addiction. The smallest available dose – a 5-mg tablet – is 3-4 times more potent than a 5-mg pill of oxycodone. So patients placed on 5 mg per day of methadone are really being started at 3 times the usual starting dose of oxycodone, hydrocodone, or morphine. And 60 mg of methadone is really more like 200 mg of oxycodone.

An opiate-naive individual should be started on half a 5-mg tablet of methadone twice daily for 2 weeks. Titration should then proceed very slowly, since it takes about 2 weeks for each new dose to reach steady state.

"There’s a weird Catch-22 situation with methadone where on the one hand it’s a short-acting drug in terms of its analgesic effect and needs to be dosed at least 3 times a day, but on the other hand it has this very long-acting risk potential," the internist observed.

The burgeoning shift from away from prescribing oxycodone in favor of methadone for chronic pain is fueled by a general recognition that something has gone very much awry nationally with regard to opiate prescribing. Prescriptions for opiates have tripled in the last 10 years. Surveys indicate 1 in 20 American adults has taken prescription opiates to get high. Most disturbingly, the annual number of unintentional fatal overdoses attributed to prescription opiates now exceeds those from heroin and cocaine combined.

Of note, Dr. Gaster observed, these unintentional fatal opiate overdoses very rarely occur in individuals who are on a single somnolence-inducing medication. The classic setup is the patient who is on an opioid for chronic pain, but who is also drinking alcohol, taking a benzodiazepine, and has sleep apnea.

He reported having no financial conflicts.

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